Background: The Global Burden of Disease study projected that depression will be the second leading cause of disability worldwide by 2020, and there is substantial (but not unequivocal) data from community studies indicating that it is a key risk factor for mortality. Both older veterans and newly returning veterans have high mental health service needs, and VA patients are particularly vulnerable, with higher rates of depression (~12% prevalence), poverty, comorbid medical illness, and disability than the general US population. The proposed study builds on our existing research on the impact of depression on Veteran suicide (IIR 04-211) and cost-effectiveness of VA depression treatment (CD2 07-206) to examine all causes of death associated with depression among VA service users. Our research team is uniquely qualified and has the necessary data resources and expertise to examine overall death rates as well as deaths from specific causes while accounting for baseline and time-varying risk factors and other potentially influential sociodemographic and clinical characteristics through its extensive administrative, survey, and cause of death data sources. Objectives: The objectives of this study are: 1) to examine the potential risks of all-cause and cause-specific mortality associated with depression among VA patients, 2) to characterize the impact of modifiable health behaviors on the relationships between depression and all-cause mortality, and mortality due to cardiovascular disease and cancer, and 3) to examine the associations between receipt of depression treatment and mortality. Methods: To achieve these objectives, we will create a new panel dataset with health and sociodemographic information on all VA service users nationwide (N~4,700,000) from FY03 followed for up to five years. We will conduct analyses with merged secondary data from existing data sources. The VA's National Patient Care Database (NPCD) will provide detailed inpatient and outpatient clinical data identifying depression and other disease diagnoses as well as health care utilization including prescription medications. Medicare utilization data will be linked for eligible patients. The National Death Index (NDI) will provide mortality data, including cause and date of death. The 2003 Survey of Healthcare Experiences of Patients (SHEP) will provide sociodemographic and health behavior information not available from administrative resources. We will use survival analysis techniques, specifically Cox regression models, as well as logistic regression analysis to examine the impact of depression on timing and causes of death in our VA patient cohort. We will examine the independent association of depression with death, as well as the impact of potential confounding factors, including medical and psychiatric comorbidity, health behaviors, and sociodemographic characteristics. In analyses using statistical methods to control for possible treatment selection biases, we will examine the impact of depression treatment on mortality. In sensitivity analyses, we will examine regional variation in the relationship between depression and timing, causes, and correlates of death. Through this work, we will not only be able to provide detailed information from the largest health-system- wide cohort ever studied on how depression is associated with mortality, but we will also be creating a unique data resource that can potentially be made available for other VA researchers and policy makers to identify causes of death in the VA patient population.